Alpine Immune Sciences Presents ALPN-101 Program Data Demonstrating Potent Preclinical Activity in Arthritis and Inflammation
- Category: Antibodies
- Published on Monday, 06 November 2017 14:42
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--Poster to be Presented at 2017 ACR/ARHP Annual Meeting--
SEATTLE, WA, USA I November 6, 2017 I Alpine Immune Sciences, Inc. (NASDAQ:ALPN), a leading immunotherapy company focused on developing treatments for autoimmune diseases and cancer, today announced results from preclinical studies evaluating ALPN-101 program dual ICOS/CD28 antagonists generated by the company’s variant immunoglobulin (Ig) domain (vIgD) platform. The ICOSL vIgD-Fc fusion proteins demonstrated potent activity in an animal model of inflammatory arthritis and in a humanized model of graft vs. host disease (GvHD). Findings suggest molecules from the company’s vIgD platform could potentially have clinical therapeutic utility in multiple inflammatory diseases. The data were presented today in a poster session titled “Rheumatoid Arthritis – Animal Models Poster II” [#1328] at the 2017 American College of Rheumatology/Association of Rheumatology Health Professionals (ACR/ARHP) Annual Meeting in San Diego, CA.
“These preclinical studies suggest our ALPN-101 program vIgDs can potently reduce pathogenic T cell activation, inflammatory cytokines, and disease activity in multiple inflammatory diseases,” said Stanford Peng, M.D., Ph.D., Executive Vice President of Research and Development and Chief Medical Officer of Alpine.
The immunoglobulin superfamily (IgSF) is a large, diverse family of proteins expressed on immune cells and collectively plays critical roles in immune regulation. Well-known IgSF proteins include PD-1, PD-L1, CTLA-4, CD28, CD80/CD86 (B7-1/2), inducible T cell costimulator (ICOS), and TIGIT. Most therapeutic strategies targeting this family of proteins have employed monoclonal antibodies binding to a single target.
In contrast, Alpine’s vIgD platform transforms natural IgSF proteins into multifunctional protein domains. CD28 and ICOS are expressed on T cells, interacting with CD80/CD86 and ICOS ligand (ICOSL), respectively, and play critical roles in T cell activation. Alpine’s ICOSL vIgD-Fcs bind and inhibit both ICOS and CD28 co-stimulatory pathways.
Evaluations included a mouse model of inflammatory arthritis and a humanized mouse model of GvHD. Belatacept, an immunosuppressive T-cell co-stimulation blocker approved by the U.S. Food and Drug Administration (FDA) to prevent kidney transplant rejection, and abatacept, approved by the FDA to treat rheumatoid, psoriatic, and juvenile idiopathic arthritis, were used as comparators.
Preclinical Study Results
Presented data from the ICOSL vIgD-Fcs:
- Inhibited multiple parameters of disease in inflammatory arthritis including reducing paw swelling, inflammatory cell infiltrates, circulating inflammatory cytokines, anti-collagen autoantibodies, and lymph node follicular helper T cells, B cells, and activated T cells.
- Prolonged survival and reduced disease activity in GvHD.
- Appeared superior to abatacept in arthritis based on clinical scores and histology, and to belatacept in GvHD based on disease activity scores and survival.
“We are encouraged by the preclinical data generated to date. The vIgD platform can produce novel, potent IgSF-based immuno-modulators whose efficacy has the potential to exceed existing approved therapies,” said Mitchell H. Gold, M.D., Executive Chairman and Chief Executive Officer of Alpine.
About Alpine Immune Sciences, Inc.
Alpine Immune Sciences, Inc. is focused on developing novel protein-based immunotherapies using its proprietary variant Ig Domain (vIgD) platform technology. The vIgD platform is designed to interact with multiple targets including many present in the immune synapse. Alpine’s vIgDs are developed using a process known as directed evolution, which produces proteins capable of either enhancing or diminishing an immune response and thereby may potentially apply therapeutically to cancer, autoimmune and inflammatory diseases. Alpine has also developed Transmembrane Immunomodulatory Protein (TIP) technology, based on the vIgD platform, to potentially enhance engineered cellular therapies. For more information, visit www.alpineimmunesciences.com.
SOURCE: Alpine Immune Sciences